核素-抗AFP抗体-MMC双弹头导向治疗肝癌的实验和临床研究  被引量:11

Expermental and clinical study on targeting treatment of liver cancer using radionuclide-anti-AFP antibody-MMC double bullet

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作  者:吴英德[1] 宋向群[1] 周德南[2] 胡晓桦[1] 甘友全[2] 李志革[1] 廖萍[1] 

机构地区:[1]广西医科大学附属肿瘤医院化疗科,广西南宁市530021 [2]广西肿瘤防治研究所

出  处:《世界华人消化杂志》1999年第5期387-390,共4页World Chinese Journal of Digestology

基  金:国家"八五"科技攻关资助课题!85-914-02-05

摘  要:目的分析标记物核素-抗AFP抗体-MMC.在荷瘤裸鼠肝癌模型的免疫显象和治疗,以及患者体内代谢、药代动力学和治疗效果方法用改良氯胺T法和过碘酸钠氧化法,直接将[3]Ⅰ(或125Ⅰ)和丝裂霉素(MMC)双标记单抗(mAb)和多抗(pAb)得标记物[3]Ⅰ-抗AFPmAb-MMC(双弹头Ⅰ)和[3]Ⅰ(或125Ⅰ)-抗AFP-pAb-MMMC(双弹头Ⅱ),将双弹头作荷瘤裸鼠定位显象和治疗,观察药物在体内代谢和药代动力学;并经静脉(V)或动脉(A)给药治疗中晚期肝癌41例(治疗组)治疗1,2,3次分别有4,24和13例,其放射剂量(MBq/例)分别为198±38,652±202和998±221结果双弹头Ⅰ,Ⅱ在肝癌模型给药d5时瘤内定位显象均清晰,d13抑瘤率分别为81.5%和50.0%、双弹头Ⅰ,Ⅱ在血浆清除T1/2约24h,尿T1/2MAb(120h)长于pAh(18h)药代动力学模式为二室模式;肝SPECT扫描肿瘤阳性显象率100%治后瘤小率、AFP下降率和一、二年生存率分别高于同期经A灌注(TAI)或化疗栓塞(TACE)的对照组(57.5%比31.7%,P<0.01;65.7%比37.5%,P<0.01和?AIM To study the radioimmunoimaging (RII) and radioimmunotherapy (RIT) for nude mice bearing human hepatocellular carcinoma (HCC), and patients with HCC weretreated by radiochemoconjugated antibody.METHODS Nuclide [3] l-anti-human AFP monoclonal antibody (anti--AFPmAb)--mitomycin C (MMC) (double bombI) and [3] 1 (or 125I)-anti-human AFP polyclonal antibody(anti--AFPpAb)--MMC (double bomb II ) were prepared bythe modified chloramine T method and sodium periodateoxidation method. After injection of lab6led drug intraperitioneally (ip), RII and RIT were Performed with gammacamera and radioactivity of the tumor was calculated.Blood pharmacokinetics in 41 Patients with unresectableHCC was analyzed, who were treated tv (n = 33) or ia (n= 8) (treatment group). Among them 4, 24 and 13 patientswere treated 1, 2 and 3 times respectively, and the median values of the radiation dose (MBq/ case) were 198 46,652 202 and 998 220 respectively.RESULTS Selective accumulation was observed in tumorsites of nude mice bearing HCC on day 3 and a clear imageof tumor was shown in gamma camera on day 5. On day17, the tumor growth inhibition rates of 'double bomb Iand II'were 76 .4% and 73. 5 %, respectively. The microcomputer graphic portrayal met a two compartment for allpatients. RII in patients by SPECT scaning showed that alltumors had positive imaging on the 5th day after injectionof labeled drug. The shrinksge rate of tumor, decreaselevel of AFP and the 1- and 2-year survival rates were significantly higher than those of the control group (n = 41 )with transarterial infusion (TAI) or transarterial chemoembOlization (TACE) in patients with HCC at the sametime (57.5%, 23/ 40 vs 31 .7%, 13/ 41, P< 0.01; 65.7%,23/35 vs 37.5%, 12/ 32, P < 0.01 and 58.5% vs 36.7%,45 .0% vs 19 .0%, P < 0. 05, respectively). Furthermore,the tumor progression rate (9. 8% ) in the treatment groupwas significantly lower than that of the control group(35 .0%, p<0.01 ).CONCLUSION [3] 1--anti--AFP antibodyuMMC has a better affinity and target--therapy is be

关 键 词:肝肿瘤 放射免疫治疗 放射性核素 丝裂霉素C 

分 类 号:R735.705[医药卫生—肿瘤] R730.59[医药卫生—临床医学]

 

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